Diagnosis CMT

The first treatable form of CMT?

I wrote this brief article on the way the SORD gene works (or fails to work) for the Hereditary Neuropathy Foundation. SORD mutations cause “the most common autosomal recessive form of CMT2 (CMT2A1), autosomal recessive intermediate CMT (CMTRIA), and the overlapping category of distal hereditary motor neuropathy (dHMN).”

As I explain in the article, “CMT2 and dHMN are under-diagnosed rare disease categories, and up to nearly 10% of the cases that fall within them may be SORD-related.”

The way this type of CMT works — the way nerves are damaged in it — has to do with the body’s inability to produce sorbitol dehydrogenase (SDH), an enzyme the SORD gene encodes. Without SDH your body can’t convert sorbitol into fructose, which is a key part of that’s known as “the polyol pathway.” (This is how glucose is converted to sorbitol and then to fructose.) When sorbitol builds up too much in cells, they can be damaged and destroyed. This appears to happen to mitochondria in nerves, leading to the type of largely axonal damage that characterizes this type of CMT. (The exact mechanism of the damage is not known yet.) Reducing sorbitol levels in people with SORD Deficiency should be possible using existing drugs for diabetics — Applied Therapeutics is working on it.

Sorbitol dehydrogenase deficiency with peripheral neuropathy (SORDD) may end up with a treatment, but it may not be classified as CMT at that point.

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